a-d, cFos reactivation in task-specific neurons expressing mCherry or hM4Di-mCherry. Overlap between cFos and mCherry in the cortex (a) and hippocampus (c) of mice injected with CNO during testing in the Morris water maze at 13 weeks of age. Quantification of mCherry+ cells and reactivation from cortex (b) and hippocampus (d) in WT (n = 4) and Rett (n = 4) mice. Scale bar, 200 μm. e, The effect of removing CNO on Morris water maze performance in WT mCherry (n = 6), Rett mCherry (n = 5), WT hM4Di (n = 5), and Rett hM4Di (n = 6) mice at 13 weeks of age. The sample size (n) corresponds to the number of biologically independent mice. 3–4 sections were analyzed per mouse. Data are represented as mean ± s.e.m. Statistical significance was determined using a two-way ANOVA with Tukey’s multiple comparisons test; ns (p>0.05), * (p<0.05), **** (p<0.0001).